Halogen bonding is a recently rediscovered secondary interaction that shows potential to become a complementary molecular tool to hydrogen bonding in rational drug design and in material sciences. Whereas hydrogen bond symmetry has been the subject of systematic studies for decades, the understanding of the analogous three-center halogen bonds is yet in its infancy. The isotopic perturbation of equilibrium (IPE) technique with (13)C NMR detection was applied to regioselectively deuterated pyridine complexes to investigate the symmetry of [N-I-N](+) and [N-Br-N](+) halogen bonding in solution. Preference for a symmetric arrangement was observed for both a freely adjustable and for a conformationally restricted [N-X-N](+) model system, as also confirmed by computation on the DFT level. A closely attached counterion is shown to be compatible with the preferred symmetric arrangement. The experimental observations and computational predictions reveal a high energetic gain upon formation of symmetric, three-center four-electron halogen bonding. Whereas hydrogen bonds are generally asymmetric in solution and symmetric in the crystalline state, the analogous bromine and iodine centered halogen bonds prefer symmetric arrangement in solution.

The first investigation of halogen bond symmetry is presented. In contrast to related hydrogen bonds, the iodous halogen bond is symmetric in solution and in the crystal. The bromous analogue is symmetric in solution, but shows asymmetry in the solid state. NMR results are in agreement with DFT predictions.